This manuscript describes a novel class of N-acylhydrazone (NAH) derivatives that act as histone deacetylase (HDAC) 6/8 dual inhibitors and were designed from the structure of trichostatin A (1). ...Para-substituted phenyl-hydroxamic acids presented a more potent inhibition of HDAC6/8 than their meta analogs. In addition, the effect of compounds (E)-4-((2-(4-(dimethylamino)benzoyl)hydrazono)methyl)-N-hydroxybenzamide (3c) and (E)-4-((2-(4-(dimethylamino)benzoyl)-2-methylhydrazono)methyl)-N-hydroxybenzamide (3f) on the acetylation of α-tubulin revealed an increased level of acetylation. These two compounds also affected cell migration, indicating their inhibition of HDAC6. An analysis of the antiproliferative activity of these compounds, which presented the most potent activity, showed that compound 3c induced cell cycle arrest and 3g induced apoptosis through caspase 3/7 activation. These results suggest HDAC6/8 as a potential target of future molecular therapies for cancer.
Few population-based data on the prevalence of eating disorders exist, and such data are especially needed because of changes to diagnoses in the DSM-5. This study aimed to provide lifetime and ...12-month prevalence estimates of DSM-5–defined anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) from the 2012–2013 National Epidemiologic Survey on Alcohol and Related Conditions.
A national sample of 36,306 U.S. adults completed structured diagnostic interviews (Alcohol Use Disorder and Associated Disabilities Interview Schedule-5).
Prevalence estimates of lifetime AN, BN, and BED were 0.80% (SE 0.07%), 0.28% (SE 0.03%), and 0.85% (SE 0.05%), respectively. Twelve-month estimates for AN, BN, and BED were 0.05% (SE 0.02%), 0.14% (SE 0.02%), and 0.44% (SE 0.04%). The odds of lifetime and 12-month diagnoses of all three eating disorders were significantly greater for women than for men after adjusting for age, race and/or ethnicity, education, and income. Adjusted odds ratios (AORs) of lifetime AN diagnosis were significantly lower for non-Hispanic black and Hispanic respondents than for white respondents. AORs of lifetime and 12-month BN diagnoses did not differ significantly by race and/or ethnicity. The AOR of lifetime, but not 12-month, BED diagnosis was significantly lower for non-Hispanic black respondents relative to that of non-Hispanic white respondents; AORs of BED for Hispanic and non-Hispanic white respondents did not differ significantly. AN, BN, and BED were characterized by significant differences in age of onset, persistence and duration of episodes, and rates of current obesity and psychosocial impairment.
These findings for DSM-5–defined eating disorders, based on the largest national sample of U.S. adults studied to date, indicate some important similarities to and differences from earlier, smaller nationally representative studies.
The recent advancements in high-throughput sequencing have resulted in the availability of annotated genomes, as well as of multi-omics data for many living organisms. This has increased the need for ...graphic tools that allow the concurrent visualization of genomes and feature-associated multi-omics data on single publication-ready plots.
We present chromoMap, an R package, developed for the construction of interactive visualizations of chromosomes/chromosomal regions, mapping of any chromosomal feature with known coordinates (i.e., protein coding genes, transposable elements, non-coding RNAs, microsatellites, etc.), and chromosomal regional characteristics (i.e. genomic feature density, gene expression, DNA methylation, chromatin modifications, etc.) of organisms with a genome assembly. ChromoMap can also integrate multi-omics data (genomics, transcriptomics and epigenomics) in relation to their occurrence across chromosomes. ChromoMap takes tab-delimited files (BED like) or alternatively R objects to specify the genomic co-ordinates of the chromosomes and elements to annotate. Rendered chromosomes are composed of continuous windows of a given range, which, on hover, display detailed information about the elements annotated within that range. By adjusting parameters of a single function, users can generate a variety of plots that can either be saved as static image or as HTML documents.
ChromoMap's flexibility allows for concurrent visualization of genomic data in each strand of a given chromosome, or of more than one homologous chromosome; allowing the comparison of multi-omic data between genotypes (e.g. species, varieties, etc.) or between homologous chromosomes of phased diploid/polyploid genomes. chromoMap is an extensive tool that can be potentially used in various bioinformatics analysis pipelines for genomic visualization of multi-omics data.
To verify weather mangroves act as sinks for marine litter, we surveyed through visual census 20 forests along the Red Sea and the Arabian Gulf, both in inhabited and remote locations. Anthropogenic ...debris items were counted and classified along transects, and the influence of main drivers of distribution were considered (i.e. land-based and ocean-based sources, density of the forest and properties of the object). We confirmed that distance to major maritime traffic routes significantly affects the density of anthropogenic debris in Red Sea mangrove forests, while this was independent of land-based activities. This suggests ocean-based activities combined with surface currents as major drivers of litter in this basin. Additionally, litter was more abundant where the mangrove density was higher, and object distribution through the mangrove stand often depended on their shape and dimension. We particularly show that pneumatophores act as a sieve retaining large plastic objects, leading to higher plastic mass estimates in mangroves compared to those of beaches previously surveyed in the Red Sea.
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•Surveys aimed at quantifying anthropogenic debris in mangroves stands are scarce.•Mangroves are sinks for marine litter and traps for land originated litter.•Mangroves aerial roots act as a sieve that retains large objects.•Large plastic objects are more frequent in mangroves than on beaches.
Mangrove forests, through pneumatophores, are filters that retain large floating plastic objects and therefore constitute a sink of marine plastic pollution.
Migraine is a highly disabling neurovascular disorder characterized by a severe headache (associated with nausea, photophobia and/or phonophobia), and trigeminovascular system activation involving ...the release of calcitonin-gene related peptide (CGRP). Novel anti-migraine drugs target CGRP signaling through either stimulation of 5-HT1F receptors on trigeminovascular nerves (resulting in inhibition of CGRP release) or direct blockade of CGRP or its receptor. Lasmiditan is a highly selective 5-HT1F receptor agonist and, unlike the triptans, is devoid of vasoconstrictive properties, allowing its use in patients with cardiovascular risk. Since lasmiditan can actively penetrate the blood-brain barrier, central therapeutic as well as side effects mediated by 5-HT1F receptor activation should be further investigated. Other novel anti-migraine drugs target CGRP signaling directly. This neuropeptide can be targeted by the monoclonal antibodies eptinezumab, fremanezumab and galcanezumab, or by CGRP-neutralizing L-aptamers called Spiegelmers. The CGRP receptor can be targeted by the monoclonal antibody erenumab, or by small-molecule antagonists called gepants. Currently, rimegepant and ubrogepant have been developed for acute migraine treatment, while atogepant is studied for migraine prophylaxis. Of these drugs targeting CGRP signaling directly, eptinezumab, erenumab, fremanezumab, galcanezumab, rimegepant and ubrogepant have been approved for clinical use, while atogepant is in the last stage before approval. Although all of these drugs seem highly promising for migraine treatment, their safety should be investigated in the long-term. Moreover, the exact mechanism(s) of action of these drugs need to be elucidated further, to increase both safety and efficacy and to increase the number of responders to the different treatments, so that all migraine patients can satisfactorily be treated.
Objective
To examine psychiatric and somatic correlates of DSM‐5 eating disorders (EDs)—anorexia nervosa (AN), bulimia nervosa (BN), and binge‐eating disorder (BED)—in a nationally representative ...sample of adults in the United States.
Method
A national sample of 36,309 adult participants in the national epidemiologic survey on alcohol and related conditions III (NESARC‐III) completed structured diagnostic interviews (AUDADIS‐5) to determine psychiatric disorders, including EDs, and reported 12‐month diagnosis of chronic somatic conditions. Prevalence of lifetime psychiatric disorders and somatic conditions were calculated across the AN, BN, and BED groups and a fourth group without specific ED; multiple logistic regression models compared the likelihood of psychiatric/somatic conditions with each specific ED relative to the no‐specific ED group.
Results
All three EDs were associated significantly with lifetime mood disorders, anxiety disorders, alcohol and drug use disorders, and personality disorders. In all three EDs, major depressive disorder was the most prevalent, followed by alcohol use disorder. AN was associated significantly with fibromyalgia, cancer, anemia, and osteoporosis, and BED with diabetes, hypertension, high cholesterol, and triglycerides. BN was not associated significantly with any somatic conditions.
Conclusions
This study examined lifetime psychiatric and somatic correlates of DSM‐5 AN, BN, and BED in a large representative sample of U.S. adults. Our findings on significant associations with other psychiatric disorders and with current chronic somatic conditions indicate the serious burdens of EDs. Our findings suggest important differences across specific EDs and indicate some similarities and differences to previous smaller studies based on earlier diagnostic criteria.
Evidence for pollinator declines largely originates from mid-latitude regions in North America and Europe. Geographical heterogeneity in pollinator trends combined with geographical biases in ...pollinator studies can produce distorted extrapolations and limit understanding of pollinator responses to environmental changes. In contrast with the declines experienced in some well-investigated European and North American regions, honeybees seem to have increased recently in some areas of the Mediterranean Basin. Because honeybees can have negative impacts on wild bees, it was hypothesized that a biome-wide alteration in bee pollinator assemblages may be underway in the Mediterranean Basin involving a reduction in the relative number of wild bees. This hypothesis was tested using published quantitative data on bee pollinators of wild and cultivated plants from studies conducted between 1963 and 2017 in 13 countries from the European, African and Asian shores of the Mediterranean Sea. The density of honeybee colonies increased exponentially and wild bees were gradually replaced by honeybees in flowers of wild and cultivated plants. The proportion of wild bees at flowers was four times greater than that of honeybees at the beginning of the period, the proportions of both groups becoming roughly similar 50 years later. The Mediterranean Basin is a world biodiversity hotspot for wild bees and wild bee-pollinated plants, and the ubiquitous rise of honeybees to dominance as pollinators could in the long run undermine the diversity of plants and wild bees in the region.
Objective
To investigate olfactory dysfunction (OD) in patients with mild coronavirus disease 2019 (COVID‐19) through patient‐reported outcome questionnaires and objective psychophysical testing.
...Methods
COVID‐19 patients with self‐reported sudden‐onset OD were recruited. Epidemiological and clinical data were collected. Nasal complaints were evaluated with the sinonasal outcome‐22. Subjective olfactory and gustatory status was evaluated with the National Health and Nutrition Examination Survey. Objective OD was evaluated using psychophysical tests.
Results
Eighty‐six patients completed the study. The most common symptoms were fatigue (72.9%), headache (60.0%), nasal obstruction (58.6%), and postnasal drip (48.6%). Total loss of smell was self‐reported by 61.4% of patients. Objective olfactory testings identified 41 anosmic (47.7%), 12 hyposmic (14.0%), and 33 normosmic (38.3%) patients. There was no correlation between the objective test results and subjective reports of nasal obstruction or postnasal drip.
Conclusion
A significant proportion of COVID‐19 patients reporting OD do not have OD on objective testing.
Trehalose 6-phosphate (Tre6P), the intermediate of trehalose biosynthesis, is an essential signal metabolite in plants, linking growth and development to carbon status. The Suc-Tre6P nexus model ...postulates that Tre6P is both a signal and negative feedback regulator of Suc levels, forming part of a mechanism to maintain Suc levels within an optimal range and functionally comparable to the insulin-glucagon system for regulating blood Glc levels in animals. The target range and sensitivity of the Tre6P-Suc feedback control circuit can be adjusted according to the cell type, developmental stage, and environmental conditions. In source leaves, Tre6P modulates Suc levels by affecting Suc synthesis, whereas in sink organs it regulates Suc consumption. In illuminated leaves, Tre6P influences the partitioning of photoassimilates between Suc, organic acids, and amino acids via posttranslational regulation of phosphoenolpyruvate carboxylase and nitrate reductase. At night, Tre6P regulates the remobilization of leaf starch reserves to Suc, potentially linking starch turnover in source leaves to carbon demand from developing sink organs. Use of Suc for growth in developing tissues is strongly influenced by the antagonistic activities of two protein kinases: SUC-NON-FERMENTING-1-RELATED KINASE1 (SnRK1) and TARGET OF RAPAMYCIN (TOR). The relationship between Tre6P and SnRK1 in developing tissues is complex and not yet fully resolved, involving both direct and indirect mechanisms, and positive and negative effects. No direct connection between Tre6P and TOR has yet been described. The roles of Tre6P in abiotic stress tolerance and stomatal regulation are also discussed.
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